Tardive dyskinesia (TD) is an involuntary movement disorder associated with the use of neuroleptic medications. Although the disorder has become relatively common among psychiatric patients maintained on neuroleptics, there is currently no clear understanding of its pathophysiology and no effective treatment approach. Thus, the long-term objective of this application is to understand the etiology and natural history of TD. Such an understanding, we believe, will help to prevent and control this condition and its sequelae. The specific aims of the proposed research are: (1) to identify demographic, neuropsychological, medical and psychosocial risk factors for TD among chronic neuroleptic users; (2) to describe the incidence of TD in two well-defined populations; (3) to identify prognostic factors for TD outcome; and (4) to assess current methods for defining and classifying cases of TD. Since June 1, 1985, we have been funded by NIMH to conduct interrelated studies of TD in a single source population, the outpatient division of the Connecticut Mental Health Center (CMHC), which is a state facility administered through a collaboration between Yale University and Connecticut's Department of Mental Health. Thus far, we have completed studies of TD prevalence (1), and the natural history of TD both on (2-4) and off (5,6) neuroleptic medication. In addition, a prospective study of TD incidence among 399 outpatients at risk was begun in 1985. To date, patient enrollment and biannual follow-up have proceeded according to schedule. In this competitive renewal, we are proposing to continue the incidence study of 262 subjects remaining at risk for five more years in order to increase the power for detecting TD risk factors. In addition, because there are findings suggesting differences in the rate of TD and its risk factors by severity of psychopathology and/or duration of treatment, we are proposing to apply the same design and methodology to 280 long-term hospitalized patients at Connecticut Valley Hospital (CVH) in Middletown, Connecticut, CVH treats psychotic patients who are too ill to be treated in the communities of CMHC's catchment area. Finally, we are proposing a prospective study of TD outcome among incident cases identified at CMHC and CVH in order to describe the course of disease and identify prognostic factors. Since this project focuses on the seriously mentally ill and involves a close collaboration between an academic site (CMHC) and a public-sector facility (CVH), it is submitted as a Public Academic Liaison (PAL) application.